Many formulations comprising therapeutic agents are sensitive to one or more elements or conditions which render them unstable after some period of time, for example when stored for a period of time. One such element or condition is sensitivity to one or more elements of the air, including but not limited to oxygen, in the space surrounding the formulation, such as the dead space or head space of a container containing the formulation. Another such element or condition is the presence of gases or dissolved gases in the formulation, including but not limited to oxygen, or exposure of one or more elements of the formulation to light, contaminating materials, or organisms such as bacteria. Another such condition or element is the ratio of the head space to the fill volume. Another such condition or element is the amount of a particular molecule relative to the amount of one or more components in a formulation, including but not limited to the active agent of the formulation.
Previous efforts to stabilize formulations include addition of one or more antioxidants such as BHT (butylated hydroxytoluene) or ascorbyl palmitate. Ascorbyl palmitate is generally used in oral and topical pharmaceuticals, as opposed to injectable formulations. Handbook Of Pharmaceutical Excipients 2003, American Pharmaceutical Association, Washington, D.C., USA and Pharmaceutical Press, London, UK. BHT is suggested at levels of about 0.0009 to about 0.002% for intravenous injectables in the Handbook Of Pharmaceutical Excipients (2003). It is thought that these stabilizing antioxidants are toxic at certain levels when administered to eye tissues. It would be preferable to have stable formulations that did not require additional formulation elements, including but not limited to preservatives, to retain their stability.
There is a need for formulations, including pharmaceutical formulations that retain stability of one or more of a therapeutic agent or other elements present in a formulation comprising a therapeutic agent when the formulation is stored for a period of time. There is a need for stable formulations comprising therapeutic agents that are sensitive to exposure to one or more elements of the air. There is a need for stable formulations of rapamycin.